Stem Cell Reviews and Reports最新文献

{"title":"GLP1 Mimetics and Stem Cells: An Intersection of Metabolic and Regenerative Medicine.","authors":"Mikhail G Kolonin","doi":"10.1007/s12015-026-11194-6","DOIUrl":"10.1007/s12015-026-11194-6","url":null,"abstract":"<p><p>Glucagon-like peptide-1 receptor agonists (GLP1RAs) have transformed the treatment of obesity and type 2 diabetes, but their effects extend beyond metabolic regulation. Emerging evidence suggests that GLP1R signaling influences embryonic and adult stem cell populations by regulating proliferation, survival, differentiation, and stemness, with potential implications for tissue regeneration and aging. At the same time, concerns remain regarding long-term effects on progenitor cell homeostasis, lean tissue maintenance, and reproductive health. Because most available data derive from heterogeneous preclinical studies, it remains unclear whether reported findings reflect indirect metabolic and immune effects and if they translate into meaningful clinical outcomes. This editorial highlights the growing intersection of GLP1 biology and regenerative medicine, discusses current evidence and unresolved questions, and emphasizes the need for mechanistic and clinical studies to define the impact of GLP1RAs on stem cell function and tissue regeneration.</p>","PeriodicalId":21955,"journal":{"name":"Stem Cell Reviews and Reports","volume":" ","pages":"2982-2984"},"PeriodicalIF":4.9,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148498033","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gasdermin A3 Drives Hair Graying via Ectopic Melanocyte Stem Cell Differentiation and Migration.","authors":"Haiying Guo, Xiufeng Bai, Hao Gong, Jia Tang, Yuhong Li","doi":"10.1007/s12015-026-11204-7","DOIUrl":"10.1007/s12015-026-11204-7","url":null,"abstract":"","PeriodicalId":21955,"journal":{"name":"Stem Cell Reviews and Reports","volume":" ","pages":"3392-3395"},"PeriodicalIF":4.9,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148631553","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dual-Reporter Gene-Based Multimodal Imaging for Tracking Mesenchymal Stem Cells in Diabetic Skin Wound Repair.","authors":"Xiaoyu Xu, Fujin Wang, Fangzhou Du, Qiong Deng, Qian Wei, Shuang Yu, Longjiang Zhang, Yonggang Li","doi":"10.1007/s12015-026-11212-7","DOIUrl":"10.1007/s12015-026-11212-7","url":null,"abstract":"<p><strong>Background: </strong>Diabetic foot ulcer (DFU) is a clinically challenging complication characterized by poor healing outcomes, and conventional therapies provide limited benefit. Mesenchymal stem cell (MSC) transplantation offers a promising strategy for DFU repair. However, the low survival of transplanted MSCs in the hostile wound microenvironment, coupled with the lack of real-time, non-invasive methods to track these cells in vivo, severely hampers their therapeutic efficacy and clinical translation.</p><p><strong>Methods: </strong>We engineered MSCs to co-express a dual reporter system comprising near-infrared fluorescent protein (iRFP) and ferritin heavy chain (FTH1). These modified cells were then integrated with a fibrin glue (FG) scaffold to create a unified platform that supports both multimodal imaging and therapeutic function within skin wounds. First, FTH1 overexpression enhances the antioxidant capacity of MSCs, while the FG scaffold provides structural support; this combination enhances cell survival and retention. Second, the iRFP/FTH1 dual reporter enables near-infrared fluorescence imaging and MRI-based localization, establishing a multimodal platform for real-time cell tracking.</p><p><strong>Results: </strong>In a full-thickness skin defect model in diabetic mice, multimodal imaging revealed that transplanted cells persisted in the wound area for approximately seven days. Treatment with iRFP/FTH1-MSCs/FG significantly accelerated wound closure and promoted hair follicle regeneration and angiogenesis. Additionally, local iron deposition resulting from FTH1 expression enhanced fibroblast migration and collagen synthesis, further facilitating extracellular matrix remodeling. Mechanistic studies demonstrated that this therapy drives macrophage polarization toward the anti-inflammatory M2 phenotype and activates the PI3K-AKT-VEGF signaling pathway. These complementary effects synergistically enhance tissue regeneration and systematically improve diabetic wound healing.</p><p><strong>Conclusions: </strong>Collectively, this multimodal stem cell-scaffold system effectively integrates dynamic cell tracking with stem cell therapy during skin wound repair. It addresses a critical technical gap in visualizing stem cells within the wound microenvironment and provides valuable methodological and theoretical foundations for optimizing regenerative strategies for diabetic skin wounds.</p>","PeriodicalId":21955,"journal":{"name":"Stem Cell Reviews and Reports","volume":" ","pages":"3360-3380"},"PeriodicalIF":4.9,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148727316","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Measurable Residual Disease and the Unresolved Biology of Leukemic Stem Cells.","authors":"Deepa Bhartiya, Nitu Jha, Shruti Dutta, Anish Tripathi, Ashish Tripathi","doi":"10.1007/s12015-026-11195-5","DOIUrl":"10.1007/s12015-026-11195-5","url":null,"abstract":"<p><p>Measurable residual disease (MRD) testing has transformed the management of hematologic cancers by enabling detection of residual malignant cells after therapy. Current approaches rely on qPCR and next-generation sequencing to monitor leukemia-associated somatic mutations, while multiparameter flow cytometry identifies aberrant leukemic immunophenotypes. Although these methods provide valuable prognostic and therapeutic information, MRD negativity remains an imperfect surrogate for cure. Most MRD platforms evaluate CD45+, rapidly dividing leukemic populations and fail to detect quiescent cells that may survive cytotoxic therapies which efficiently target proliferating hematopoietic cells. Relapse frequently occurs despite deep molecular remission, suggesting persistence of rare leukemic stem cells (LSCs) that are intrinsically resistant to chemotherapy and targeted therapies. The paradox of relapse despite molecular remission could be explained by the presence of very small embryonic-like stem cells (VSELs) which are pluripotent, quiescent stem cells sitting at the top of cellular hierarchy in multiple adult tissues including bone marrow. A pluripotent VSEL divides through asymmetrical cell division to give rise to two cells of different sizes and fates, smaller cell is to self-renew while the bigger is lineage-restricted and tissue-committed progenitor which undergoes extensive epigenetic changes, divides rapidly and undergoes clonal expansion before further differentiation. Dysfunctions of VSELs initiate both solid and hematologic cancers. Based on this view, somatic mutations monitored during MRD assessment possibly represent downstream consequences of clonal expansion rather than the initiating drivers of disease persistence. Thus, exclusive monitoring of somatic mutations and CD45 + leukemic populations possibly overlook rare, small-sized, CD45- VSELs that contribute to therapeutic resistance and relapse.</p>","PeriodicalId":21955,"journal":{"name":"Stem Cell Reviews and Reports","volume":" ","pages":"3406-3416"},"PeriodicalIF":4.9,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148585141","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanisms of Hematopoietic Stem Cell Aging and Emerging Rejuvenation Strategies.","authors":"Qi Liu, Lijun Zhao, Chengying Li","doi":"10.1007/s12015-026-11211-8","DOIUrl":"10.1007/s12015-026-11211-8","url":null,"abstract":"<p><p>Hematopoietic stem cell (HSCs) aging is a complex biological process driven by both cell-intrinsic alterations and extrinsic cues from the bone marrow niche. Understanding these mechanisms is critical for developing therapies against aging-related hematopoietic disorders. This review synthesizes recent advances in the molecular mechanisms underlying HSCs aging, including microenvironmental aging, genomic instability, epigenetic dysregulation, mitochondrial dysfunction, and aberrant nuclear mechanotransduction. We summarize that the functional decline of HSCs during aging drives a compensatory expansion of the phenotypically defined stem cell pool, leading to an aberrant increase in cell number. We also highlight aging-associated HSCs heterogeneity, including CD150^high and P-selectin-positive subsets that enrich for myeloid-biased or functionally compromised HSCs states while emphasizing that surface phenotype alone may not fully indicate functional rejuvenation. Finally, we discuss emerging rejuvenation strategies-including targeting myeloid-biased HSCs, modulating inflammatory pathways, and implementing epigenetic or metabolic interventions-supported by cutting-edge technologies such as single-cell multi-omics, gene editing, and computational modeling. These approaches hold promise for counteracting age-related hematopoietic decline and restoring immune competence.</p>","PeriodicalId":21955,"journal":{"name":"Stem Cell Reviews and Reports","volume":" ","pages":"3262-3280"},"PeriodicalIF":4.9,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148702119","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nanotechnology-enabled precision targeting of lung cancer stem cells: Recent developments and therapeutic implications.","authors":"Yi Zhang, Jiaxin Fan, Yuhan Ye, Chuang Li, Ming-Fei Lang","doi":"10.1007/s12015-026-11198-2","DOIUrl":"10.1007/s12015-026-11198-2","url":null,"abstract":"<p><p>Lung cancer remains one of the leading causes of cancer-related mortality worldwide, highlighting the urgent need for more effective therapeutic strategies. Lung cancer stem cells (LCSCs) play critical roles in tumor initiation, metastasis, therapeutic resistance, and recurrence through dynamic interactions with the tumor microenvironment (TME), metabolic reprogramming, and immune evasion. Despite advances in targeted therapy and immunotherapy, conventional approaches remain insufficient for the complete elimination of LCSCs. Recent progress in nanotechnology has provided new opportunities for precision targeting of LCSCs by enhancing drug bioavailability, tumor selectivity, controlled release, and multifunctional therapeutic integration. In this review, we summarize current nanotechnology-enabled strategies targeting LCSCs, with particular emphasis on TME remodeling, metabolic regulation, and tumor immunity. Distinct from previous reviews that discuss cancer stem cells or nanomedicine separately, this review establishes an integrated framework linking LCSC niche regulation with nanotechnology-based precision therapeutics in lung cancer. We further highlight the therapeutic potential of multifunctional nanoplatforms, including nanocrystalline drugs, smart nanocarriers, and combinational nano-delivery systems, in modulating stemness-associated pathways, overcoming immune suppression, and disrupting metabolic adaptation. In addition, emerging strategies involving stimulus-responsive nanomaterials, ferroptosis induction, and engineered immunotherapeutic platforms are discussed. Finally, current challenges and future perspectives regarding tumor heterogeneity, nanocarrier biocompatibility, translational feasibility, and personalized therapeutic design are addressed. Collectively, this review provides a comprehensive perspective on nanotechnology-enabled precision targeting of LCSCs and offers insights into next-generation therapeutic strategies for lung cancer.</p>","PeriodicalId":21955,"journal":{"name":"Stem Cell Reviews and Reports","volume":" ","pages":"3152-3171"},"PeriodicalIF":4.9,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148593244","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hair Follicle Stem Cells: Emerging Physiology and Therapeutic Applications.","authors":"Shuyuan Yang, Qun Chen, Hanluo Li, Guang Yang","doi":"10.1007/s12015-026-11199-1","DOIUrl":"10.1007/s12015-026-11199-1","url":null,"abstract":"<p><p>Hair follicle stem cells (HFSCs) have been studied for their role in developmental biology, hair cycling and transplantation. However, recent research reframes the hair follicle as a heterogeneous regenerative ecosystem capable of responding to injury cues and contributing to tissue repair beyond trichology. Despite advances, our understanding of HFSC physiology and therapeutic applications remains fragmented. Many reviews fail to bridge the gap between mechanistic biology and translatable therapeutic modalities, often overlooking critical aspects such as stemness-preserving culture systems, biomaterial-assisted delivery, and the specific influence of distinct wound microenvironments on HFSC fate. This review aims to delineate the current landscape of HFSC research, synthesizing evidence for their therapeutic potential beyond hair regeneration and discussing translational bottlenecks. This study summarizes core physiological functions, including injury-driven re-epithelialization and melanocyte stem cell-coupled re-pigmentation. We synthesize evidence for HFSC-based therapies in acute/chronic wounds (including diabetic and venous ulcers), burns, vitiligo, and exploratory applications in diabetes and ocular reconstruction. Furthermore, we introduce strategies for stemness-preserving expansion, preconditioning, and bioengineering delivery systems. This review provides a reference for advancing HFSC-based therapies toward reproducible, clinically viable interventions by integrating physiological insights with engineering solutions to overcome current translational barriers.</p>","PeriodicalId":21955,"journal":{"name":"Stem Cell Reviews and Reports","volume":" ","pages":"3172-3195"},"PeriodicalIF":4.9,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148607556","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Overcoming Immunological Barriers in MSC-Derived Insulin-Producing Cells through CRISPR-Based Hypoimmunogenic Engineering and Translational Perspectives for Type 1 Diabetes.","authors":"Zahid Yaseen, Mothilal M","doi":"10.1007/s12015-026-11184-8","DOIUrl":"10.1007/s12015-026-11184-8","url":null,"abstract":"<p><p>Mesenchymal stromal cell (MSC)-derived insulin-producing cells (IPCs) represent an emerging strategy for β-cell replacement in type 1 diabetes mellitus (T1DM) owing to their differentiation potential, intrinsic immunomodulatory properties, and lower tumorigenic risk compared with pluripotent stem cell-derived platforms. However, accumulating evidence indicates that differentiation-associated immunogenicity, context-dependent immune recognition, and recurrent autoimmune responses may substantially limit long-term graft survival and therapeutic durability following transplantation. This review critically examines the immunological barriers associated with MSC-derived IPCs, including altered MHC expression, susceptibility to alloimmune and autoimmune-mediated rejection, and potential reactivation of autoreactive immune memory. We discuss the application of CRISPR-based hypoimmunogenic engineering strategies targeting antigen presentation pathways, NK-cell activation, and immune checkpoint modulation to generate more immune-evasive MSC-derived IPCs while preserving β-cell functionality. By integrating insights from T1DM immunopathogenesis, MSC biology, genome editing, and translational immunology, we propose a framework linking immune engineering with controlled differentiation, functional maturation, and long-term safety evaluation. In parallel, we comparatively position MSC-derived IPCs alongside clinically advancing iPSC-derived β-cell platforms to highlight their distinct translational niche, including potential advantages related to safety, immunomodulatory capacity, manufacturing accessibility, and scalability, while acknowledging the superior functional maturity and clinical progression currently demonstrated by iPSC-derived systems. Finally, we discuss key translational challenges, including genomic stability, immune-evasion durability, GMP-compliant manufacturing, and the need for rigorous functional and immunological benchmarking prior to clinical application of hypoimmunogenic MSC-derived IPC therapies in T1DM.</p>","PeriodicalId":21955,"journal":{"name":"Stem Cell Reviews and Reports","volume":" ","pages":"3033-3055"},"PeriodicalIF":4.9,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148369586","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neutrophils: The Overlooked Regenerative Role in Bone Repair.","authors":"Yumeng Lin, Yuchen He, Quan Yuan, Shiwen Zhang","doi":"10.1007/s12015-026-11203-8","DOIUrl":"10.1007/s12015-026-11203-8","url":null,"abstract":"<p><p>Bone repair is a complex regenerative process involving inflammatory responses, vascular remodeling, and stem cell-mediated osteogenesis, wherein the immune microenvironment plays a critical regulatory role. Neutrophils have long been recognized as short-lived, pro-inflammatory effector cells primarily responsible for pathogen clearance and tissue debridement, and may even trigger inflammatory tissue damage when abnormally activated. Their regenerative potential in bone healing has, therefore, been significantly underestimated. Emerging evidence suggests that neutrophils are pivotal contributors to the bone repair process, exhibiting remarkable functional diversity that extends beyond their classical inflammatory roles. During the repair process, neutrophils assist in extracellular matrix (ECM) deposition and secrete pro-angiogenic factors, thereby fostering the early repair microenvironment. Meanwhile, they modulate the immune microenvironment through bidirectional interactions with macrophages and other immune cells, and promote bone regeneration by facilitating the recruitment and osteogenic differentiation of bone marrow mesenchymal stem cells (BM-MSCs). Recent studies have also begun to elucidate the temporal dynamics and circadian regulation of neutrophil functions during tissue repair. Conversely, under pathological conditions, aberrantly activated neutrophils can disrupt these finely tuned processes and drive pathological bone repair. Collectively, these findings necessitate a redefinition of the role of neutrophils in bone repair and underscore the importance of exploring new concepts and directions in neutrophil biology.</p>","PeriodicalId":21955,"journal":{"name":"Stem Cell Reviews and Reports","volume":" ","pages":"3209-3226"},"PeriodicalIF":4.9,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148631529","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Human Umbilical Cord Mesenchymal Stem Cells in Metabolic Dysfunction-associated Fatty Liver Disease (MAFLD) Therapy: Mechanisms, Clinical Efficacy, and Future Perspectives.","authors":"Hua Jiang, Hui Wang, Yankun Zhu, Chunyan Yi, Jinli Liu, Ruisi Zhao, Jianpeng Gao, Anmin Cao, Yangfan Guo","doi":"10.1007/s12015-026-11181-x","DOIUrl":"10.1007/s12015-026-11181-x","url":null,"abstract":"<p><p>There is currently no approved drug treatment for metabolic dysfunction-related fatty liver disease (MAFLD). Umbilical cord-derived mesenchymal stem cells (UC-MSCs) show therapeutic potential, but their mechanism of action is remains incompletely understood. Different from previous reviews that focused on a single pathway, this article presents three important contributions: First, it constructs an integrated \"multi-target synergy network\" model, clarifying how UC-MSCs coordinate and regulate the inflammatory, metabolic and fibrotic processes through the interactions between the AMPK/mTOR, Nrf2/HO-1 and TGF-β/Smad pathways; Second, it systematically assesses recent clinical trials (2022-2025), identifying several unaddressed barriers to transformation, including the lack of histological endpoint indicators, batch-to-batch differences, and the absence of dose exploration studies; Third, we integrate the latest developments from 2024 to 2025, particularly mitochondrial transfer (mediated by tunnel nanotubes and accompanied by quantitative efficacy data) and exosome circular RNA networks [Formula: see text], which have not been covered in previous reviews. Based on the above analysis, we also propose specific suggestions for standardized GMP production, mandatory genomic stability testing, and long-term safety registration. This review provides a comprehensive analysis of elaborates on the treatment of MAFLD with UC-MSCs from a mechanistic and translational perspective, based on the extensive updates of relevant literature.</p>","PeriodicalId":21955,"journal":{"name":"Stem Cell Reviews and Reports","volume":" ","pages":"3117-3130"},"PeriodicalIF":4.9,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13550056/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148472889","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}